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FDA Approves First Prodrug for Acute Pain

For short-term yet severe pain, KemPharm’s Apadaz may offer safer opioid option

A PPM Brief

FDA recently announced the approval of Apadaz for the short-term (no more than 14 days) management of acute pain that is severe enough to require an opioid analgesic and for which alternative treatments have been deemed inadequate. Made by KemPharm (Coralville, IA), a specialty pharmaceutical company focused on proprietary prodrugs, Apadaz is an immediate-release (IR) combination of benzhydrocodone and acetaminophen.1

Photo courtesy of KemPharm, Inc, Coralville, IA

A relatively novel class of pharmaceuticals, prodrugs have the ability to offer abuse-deterrent properties. They are essentially inactive, bioreversible derivatives of active drug molecules that must undergo an enzymatic or chemical transformation to release the parent drug, which can then elicit its desired pharmacological effect in the body (read more in PPM’s just-released March 2018 issue).2 In Apadaz’s case, when ingested, enzymes in the gastrointestinal tract cleave the ligand from the prodrug (benzhydrocodone) and release the parent drug (hydrocodone), which can then exert its therapeutic effect. The final approved product labeling for Apadaz includes these data points but concludes that the overall results of the clinical program did not demonstrate abuse-deterrence by current measurement standards.However, in a comment to Practical Pain Management, KemPharm executive vice president, government and public relations Daniel Cohen said that they will be looking to obtain abuse deterrence labeling in the future.

“Based on its unique properties, we firmly believe there is a commercial pathway for Apadaz in what is a very high-volume market,” said Travis Mickle, PhD, president and chief executive officer at KemPharm in a company press release. “We are excited by the opportunity Apadaz offers to patients and for physicians who now have the option of prescribing a differentiated product.”

The approval of Apadaz is based in part on pharmacokinetic studies comparing it to similar opioids. Apadaz demonstrated exposure to hydrocodone and acetaminophen resulting in therapeutic effects equivalent to currently approved immediate-release hydrocodone/APAP combination products when administered orally.The most common adverse reactions associated with Apadaz are nausea, somnolence, vomiting, constipation, pruritus, dizziness, and headache.1

“The Apadaz approval highlights the value potential that LAT (Ligand Activated Therapy) offers in the discovery and development of proprietary prodrugs that are designed to be differentiated versions of widely-prescribed, currently-approved drugs,” Dr. Mickle concluded.

Due to the risks of addiction, abuse, and misuse with opioids, KemPharm noted that physicians should reserve Apadaz for use in patients for whom alternative treatment options such as non-opioid analgesics have not been or are not expected to be tolerated, or have not provided or are expected to provide adequate analgesia.1 More important safety information, including safety risks and drug interactions, can be found here.

Last updated on: March 14, 2018
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